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The universal bacterial second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays critical roles in regulating a variety of bacterial functions such as biofilm formation and virulence. The metabolism of c-di-GMP is inversely controlled by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs). Recently, increasing studies suggested that the protein-protein interactions between DGCs/PDEs and their partners appear to be a common way to achieve specific regulation.

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Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.

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When two signals cross paths: cGAS-STING and ER stress in kidney disease progression.

Kidney Int

February 2025

Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan. Electronic address:

Previous reports have suggested that both the endoplasmic reticulum (ER) stress and cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathways contribute to the progression of chronic kidney disease; however, the relationship between these 2 pathways in kidney injury has not been fully elucidated. Andrade-Silva et al. revealed that the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway can enhance ER stress through the protein kinase R-like ER kinase (PERK)-mediated signaling cascade in kidney tubular epithelial cells and sequentially augment fibrosis during kidney injury.

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Transport and action of sesame protein-derived ACE inhibitory peptides ITAPHW and IRPNGL.

Food Chem

January 2025

State Key Laboratory of Food Science and Resources, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China; School of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang, Jiangxi, 330047, PR China.

Vascular endothelial dysfunction is an important pathogenic factor in hypertension, in which angiotensin-converting enzyme (ACE) plays an important role. Peptides that bind to ACE may attenuate vascular endothelial dysfunction by altering the structure of ACE. This study demonstrated that ITAPHW and IRPNGL were resistant to simulated gastrointestinal fluid and were transported across the Caco-2 monolayer via the intercellular space, with ITAPHW showing a high apparent permeability coefficient of (1.

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A series of biodegradable nanoparticle-based drug delivery systems have been designed utilizing poly(β-amino ester)-guanidine-phenylboronic acid (PBAE-G) polymers. In this study, a novel Lentinan-Functionalized PBAE-G-nanodiamond system was developed to carry ovalbumin (LNT-PBAE-G-ND@OVA). The impact of this drug delivery system on the activation and maturation of macrophages was then assessed.

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